Association ofFoxp3Polymorphism With Allograft Outcome in Kidney Transplantation

Abstract

BackgroundForkhead box P3 (Foxp3) is the most reliable marker for regulatory T cells, which play an important role in maintaining renal allograft tolerance. Recently, Foxp3 polymorphisms have been reported to be associated with graft outcome in kidney transplantation. We analyzed the association of Foxp3 polymorphisms with renal allograft outcome.MethodsFoxp3 polymorphisms (rs3761548 A/C, rs2280883 C/T, rs5902434 del/ATT, and rs2232365 A/G) were tested by PCR with sequence-specific primers (PCR-SSP) in 231 adult kidney transplantation recipients from 1996-2004 at Seoul National University Hospital.ResultsPatients with the rs3761548 CC genotype showed better graft survival than those with the AC or AA genotype (log rank test, P=0.03). Patients with the rs3761548 CC genotype also showed a lower rate of recurrence of the original glomerular disease than those with the AC or AA genotype (P=0.01). The frequency of acute rejection (AR) in patients with the rs2280883 TT genotype was lower than that in patients with the rs2280883 CT or CC genotype (26.9% vs 53.3%, P=0.038). Patients with the rs2280883 TT genotype also showed better graft survival than those with the CT or CC genotype (P=0.03).ConclusionsFoxp3 rs3761548 CC and rs2280883 TT genotypes were associated with superior graft outcome of kidney transplantation. Further studies involving a larger number of patients are needed.

Diminished circulating concentration of interleukin‐35 in Helicobacter pylori‐infected patients with peptic ulcer: Its association with FOXP3 gene polymorphism, bacterial virulence factor CagA, and gender of patients

“…The mutations in FOXP3 and Treg cell deficiency result in the development of various autoimmune diseases in humans as is well described in the Immunodysregulation Polyendocrinopathy Enteropathy X‐linked (IPEX) syndrome . Moreover, some FOXP3 gene polymorphisms could affect the function and quantity of the FOXP3 protein and thus influence the Treg function, being associated with various inflammatory and autoimmune diseases . Several polymorphisms were reported in the promoter, intron, and exon regions of the FOXP3 gene .…”

“…20 Moreover, some FOXP3 gene polymorphisms could affect the function and quantity of the FOXP3 protein and thus influence the Treg function, being associated with various inflammatory and autoimmune diseases. 28 Several polymorphisms were reported in the promoter, intron, and exon regions of the FOXP3 gene. 29 The promoter is involved in initiation of transcription and therefore is among the major elements that control gene expression.…”

Impact of TBX21, GATA3, and FOXP3 gene polymorphisms on acute cellular rejection after liver transplantation

“…Finally, heterogeneous results have been documented for both SNPs. [30][31][32][33][34] In conclusion, we could not identify any association between SNPs rs4794067, rs2275806, and rs2232365 mapping in the genes of TBX21, GATA3, and FOXP3 and acute cellular liver transplant rejection. In contrast, the SNP rs3761548 (−3279C>A) of the FOXP3 gene displays an association with l-BPACR.…”

“…The other studies investigated the selected FOXP3 SNPs for association with acute rejection and graft survival in the context of kidney transplantation. Finally, heterogeneous results have been documented for both SNPs …”

Polymorphisms in mTOR and Calcineurin Signaling Pathways Are Associated With Long-Term Clinical Outcomes in Kidney Transplant Recipients

“…FOXP3 c.-22-902A>G and c.-23+2882A>C polymorphisms were not related to long term acute rejection in kidney recipients, even when the analysis was carried out considering male as hemizygous and grouping with correspondent homozygous genotypes (data not shown). A previous study also did not find association of both FOXP3 variant with acute or chronic rejection, even in a 10-years follow-up period ( Park et al, 2017 ). On the other hand, other studies reported association of the FOXP3 c.-23+2882A>C (A allele) polymorphism with long-term (2 and 5 years) acute rejection or nephrotoxicity in kidney recipients from different populations treated with cyclosporine- or TAC- based immunosuppressive therapy ( Qiu et al, 2012 ; Misra et al, 2016 ; Wu et al, 2017 ).…”